AB1477 IS HYPOPHOSPHATASIA MISDIAGNOSED IN A TERTIARY RHEUMATOLOGIC CENTRE?
Authors: Z. Boyadzhieva, B. Muche, P. Hoff, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Hypophosphatasia (HPP) is a rare disease caused by mutations of the ALPL gene leading to reduced activity of tissue non-specific alkaline phosphatase (AP). HPP can mimic other diseases clinically and be overseen, misdiagnosed or in the worst-case inadequately treated. <h3>Objectives</h3> To identify patients with a high likelihood of HPP, explore the frequency of HPP in our rheumatologic outpatient clinic and summarize clinical presentation of HPP patients. <h3>Methods</h3> Patients with measured AP levels &lt;=45 U/l between 2013 and 2022 were identified, possible HPP symptoms and lab parameters were documented. Where only one measurement of AP was available, no further analysis was undertaken. All patients with AP levels&gt;45 U/l were excluded to increase the likelihood of HPP. Those with multiple (&gt;=2) very low AP values (&lt;=35U/l) were defined as <i>suspicious for HPP</i>. After detailed chart review for secondary causes for low AP levels (e.g., severe hypothyroidism, exposure to bisphosphonates (BIS)) and exclusion of said cases, an analysis of the remaining ones followed. Where HPP was suspected, we aimed to initiate a measurement of pyridoxal phosphate (B6) within clinical routine. Elevated B6 levels (&gt;50μg/l) were used as further marker suggestive of HPP. <h3>Results</h3> 6861 AP measurements in 3362 patients were identified. 262 (7.8%) patients had at least one low AP value. The further workflow is shown in Figure 1. 28 (10.7%) patients had AP levels &lt;=35U/l at least twice. B6 measurements are available for 7 patients. Elevated values were seen in 3 of 7. In two cases HPP was confirmed genetically. The rest of the patients defined as <i>suspicious for HPP</i> presented unspecific symptoms (Fig. 1). During screening, 2 patients were identified with a previously confirmed HPP. However, the filtering strategy used here excluded these (for history of normal AP values and exposure to BIS). Details are shown in Table 1. <h3>Conclusion</h3> In our analysis of measured serum AP levels in a tertiary care centre for rheumatology we found 4 patients with definitive HPP and 1 patient with a high probability of HPP. The clinical symptoms possibly related to HPP were mild. In one case, the current diagnosis of psoriatic arthritis was documented as <i>suspected</i>; thus, the clinically leading arthralgia might be explained by HPP. All other patients had definite rheumatic diseases. Mistreatment was not found. The definitive number of patients with HPP among the cases currently defined as suspicious may be greater due to missing data on B6 in this retrospective analysis. However, only mild phenotypes were seen. Developing a universal algorithm to detect HPP remains difficult: our filtering strategy failed to identify 2 of the 4 patients with confirmed HPP. We conclude that in patients with repeatedly low serum AP levels occasionally occurring normal AP and exposure to BIS cannot rule out HPP. A further workup should include B6 levels, especially in the presence of (fragility) fractures and other symptoms not sufficiently explained by the presence of a rheumatic disease. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.